Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy

NCT ID: NCT00980954

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2025-09-04

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without additional chemotherapy in treating cervical cancer.

PURPOSE: This randomized phase III trial is studying chemotherapy and pelvic radiation therapy to see how well they work when given with or without additional chemotherapy in treating patients with high-risk early-stage cervical cancer after radical hysterectomy.

Detailed Description

OBJECTIVES:

Primary

• To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.

Secondary

• To evaluate adverse events.
• To evaluate overall survival.
• To evaluate quality of life.
• To evaluate chemotherapy-induced neuropathy.
• To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control.
• To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival.
• To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.

NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy.

• Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.

Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.

After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Conditions

Cervical Cancer

Keywords

cervical adenocarcinoma; cervical adenosquamous cell carcinoma; cervical squamous cell carcinoma; stage IA cervical cancer; stage IB cervical cancer; stage IIA cervical cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I: Cisplatin/Radiation Therapy

Standard external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) to the pelvis once daily 5 days a week for 5-6 weeks as 45 Gy in 25 fractions or 50.4 Gy in 28 fractions (1.8 Gy/fraction). Concurrent cisplatin IV over one hour once weekly for 6 weeks as 40 mg/m\^2, maximum dose 70 mg. A brachytherapy boost following radiation therapy is optional.

Group Type: ACTIVE_COMPARATOR

cisplatin

Intervention Type: DRUG

Intravenously

intensity-modulated radiation therapy

Intervention Type: RADIATION

Daily fractions

standard external beam radiation therapy

Intervention Type: RADIATION

Daily fractions

Optional brachytherapy boost

Intervention Type: RADIATION

Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.

Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

Chemoradiotherapy as in arm I, followed 4-6 weeks later by paclitaxel IV \[135 mg/m2, with maximum body surface area (BSA) of 2.0 m\^2 over 3 hours\] and carboplatin IV \[area under the curve (AUC) 5 over 30 minutes\] on day 1 of 21-day cycle for 4 cycles in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

Intravenously

cisplatin

Intervention Type: DRUG

Intravenously

paclitaxel

Intervention Type: DRUG

Intravenously

intensity-modulated radiation therapy

Intervention Type: RADIATION

Daily fractions

standard external beam radiation therapy

Intervention Type: RADIATION

Daily fractions

Optional brachytherapy boost

Intervention Type: RADIATION

Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.

Interventions

carboplatin

Intravenously

Intervention Type: DRUG

cisplatin

Intravenously

Intervention Type: DRUG

paclitaxel

Intravenously

Intervention Type: DRUG

intensity-modulated radiation therapy

Daily fractions

Intervention Type: RADIATION

standard external beam radiation therapy

Daily fractions

Intervention Type: RADIATION

Optional brachytherapy boost

Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.

Intervention Type: RADIATION

Other Intervention Names

IMRT; EBRT

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous, adenosquamous, or adenocarcinoma of the cervix with any/all of the following high-risk features after surgery:

• Positive pelvic nodes
• Positive parametrium
• Positive para-aortic nodes that have been completely resected and are positron emission tomography (PET)/computed tomography (CT) scan-negative

• PET only required if positive para-aortic nodes during surgery
• Clinical stage IA2, IB, or IIA disease (this corresponds to surgical tumor node metastasis (TNM) staging of T1-T2, N1, M0)
• Must have undergone radical hysterectomy (open, laparoscopically, or robotic) and staging within the past 70 days

• Para-aortic and pelvic node sampling required

• If the patient did not have a para-aortic lymph node sampling/dissection, but had common iliac node dissection that was negative, a PET-CT is recommended, but not required
• A negative pre- or post-operative PET scan or PET-CT scan of the para-aortic nodes is required if the patient did not undergo para-aortic or common iliac nodal sampling/dissection
• No gross residual disease
• No neuroendocrine histology
• No distant metastases

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ≥ 1,800/mm³
• Platelets ≥ 100,000/mm³
• White blood cell count (WBC) ≥ 4,000/mm³
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
• Serum creatinine ≤ 1.5 mg/dL
• Bilirubin ≤ 1.5 times upper limit of normal
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) normal
• Alkaline phosphatase normal
• Known HIV positivity allowed provided cluster of differentiation 4 (CD4) count is ≥ 350/mm³ within the past 14 days
• No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
• No severe, active co-morbidity, including any of the following:

• Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
• Transmural myocardial infarction within the past 6 months
• Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry
• Coagulation defects
• No prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy for the current cervical cancer

• Prior chemotherapy for a different cancer is allowed
• No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anuja Jhingran, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Providence Hospital

Mobile, Alabama, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Arizona Center for Cancer Care-Peoria

Peoria, Arizona, United States

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Mercy San Juan Medical Center

Carmichael, California, United States

City of Hope Medical Center

Duarte, California, United States

Saint Joseph Hospital - Orange

Orange, California, United States

Pomona Valley Hospital Medical Center

Pomona, California, United States

Mercy Cancer Center

Sacramento, California, United States

Mercy General Hospital Radiation Oncology Center

Sacramento, California, United States

University of California At San Diego

San Diego, California, United States

Saint Helena Hospital

St. Helena, California, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Memorial Healthcare System - Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Jackson Memorial Hospital-Holtz Children's Hospital

Miami, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Baptist Hospital of Miami

Miami, Florida, United States

Florida Hospital

Orlando, Florida, United States

Grady Health System

Atlanta, Georgia, United States

Northside Hospital

Atlanta, Georgia, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Saint Joseph's-Candler Health System

Savannah, Georgia, United States

Queen's Medical Center

Honolulu, Hawaii, United States

University of Hawaii

Honolulu, Hawaii, United States

Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, United States

Saint Francis Hospital and Health Centers

Beech Grove, Indiana, United States

Franciscan Saint Margaret Health-Hammond Campus

Hammond, Indiana, United States

Franciscan Saint Francis Health-Indianapolis

Indianapolis, Indiana, United States

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Mercy Medical Center - North Iowa

Mason City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Kansas City Cancer Centers-Southwest

Overland Park, Kansas, United States

Via Christi Regional Medical Center

Wichita, Kansas, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, United States

Holy Cross Hospital

Silver Spring, Maryland, United States

Hickman Cancer Center

Adrian, Michigan, United States

Saint John Hospital and Medical Center

Detroit, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Saint Joseph Mercy Port Huron

Port Huron, Michigan, United States

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Kansas City Cancer Center - South

Kansas City, Missouri, United States

Kansas City Cancer Centers - North

Kansas City, Missouri, United States

Kansas City Cancer Center-Lee's Summit

Lee's Summit, Missouri, United States

Phelps County Regional Medical Center

Rolla, Missouri, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Saint John's Mercy Medical Center

St Louis, Missouri, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

The Nebraska Medical Center

Omaha, Nebraska, United States

Elliot Hospital

Manchester, New Hampshire, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Morristown Memorial Hospital

Morristown, New Jersey, United States

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

Mount Holly, New Jersey, United States

UMDNJ - New Jersey Medical School

Newark, New Jersey, United States

MD Anderson Cancer Center at Cooper-Voorhees

Voorhees Township, New Jersey, United States

State University of New York Downstate Medical Center

Brooklyn, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Highland Hospital

Rochester, New York, United States

University of Rochester

Rochester, New York, United States

Montefiore Medical Center-Weiler Division

The Bronx, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Akron General Medical Center

Akron, Ohio, United States

Summa Barberton Hospital

Barberton, Ohio, United States

University of Cincinnati

Cincinnati, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Summa Health Center at Lake Medina

Medina, Ohio, United States

UHHS-Chagrin Highlands Medical Center

Orange, Ohio, United States

Southern Ohio Medical Center

Portsmouth, Ohio, United States

Robinson Radiation Oncology

Ravenna, Ohio, United States

Cancer Care Center, Incorporated

Salem, Ohio, United States

Ireland Cancer Center at Firelands Regional Medical Center

Sandusky, Ohio, United States

Flower Hospital

Sylvania, Ohio, United States

University of Toledo

Toledo, Ohio, United States

UHHS-Westlake Medical Center

Westlake, Ohio, United States

Cancer Treatment Center

Wooster, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Providence Portland Medical Center

Portland, Oregon, United States

Providence Saint Vincent Medical Center

Portland, Oregon, United States

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, United States

Reading Hospital

West Reading, Pennsylvania, United States

Lankenau Hospital

Wynnewood, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Sanford Cancer Center-Oncology Clinic

Sioux Falls, South Dakota, United States

University of Tennessee - Knoxville

Knoxville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Methodist Hospital

Houston, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

McKay-Dee Hospital Center

Ogden, Utah, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Dixie Medical Center Regional Cancer Center

St. George, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

Wheeling Hospital

Wheeling, West Virginia, United States

Saint Vincent Hospital

Green Bay, Wisconsin, United States

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Aurora West Allis Medical Center

West Allis, Wisconsin, United States

McGill University Department of Oncology

Montreal, Quebec, Canada

Pamela Youde Nethersole Eastern Hospital

Chai Wan, , Hong Kong

Seoul National University Bundang Hospital

Seongnam, Kyeonggi-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Gangnam Severance Hospital

Seoul, , South Korea

Korea Cancer Center Hospital

Seoul, , South Korea

Countries

China; United States; Canada; Hong Kong; South Korea

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CDR0000654709

Identifier Type: -

Identifier Source: secondary_id

NCI-2011-01973

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG 0724/GOG-0724

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0724

Identifier Type: -

Identifier Source: org_study_id